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Localization of clusterin in the epimembranous deposits of passive Heymann nephritis
Abstract:
The membrane attack complex of complement (MAC) plays an important role in the mediation of proteinuria in experimental membranous nephropathy induced by Heymann antiserum. SP-40,40 is a recently described serum protein which appears to inhibit the formation of cytolytic MAC in a manner analogous to S protein/vitronectin. SP-40,40 is homologous to proteins originally isolated from rat and ram seminal fluid (sulfated glycoprotein 2 and clusterin, respectively). By current convention, these proteins are considered clusterin homologues. The objective of this study was to examine the participation of rat clusterin in passive Heymann nephritis. Using an antibody to rat clusterin as an immunofluorescent probe, clusterin deposits were demonstrated along the glomerular capillary wall in an identical pattern to rat C3 and C5b-9. Decomplementation using cobra venom factor prevented proteinuria and intraglomerular MAC formation. The epimembranous clusterin were not detected in the complement-depleted animals. The role of clusterin in the mediation of glomerular injury remains unknown, but it is probably related to in situ formation of the terminal complement cascade where it may play a regulatory role.
Insights
Rat clusterin deposits on glomerular capillaries during experimental membranous nephropathy, suggesting a role in the terminal complement cascade and proteinuria development.
Area of Science:
- Immunology
- Nephrology
- Complement System Biology
Background:
- The membrane attack complex of complement (MAC) is implicated in proteinuria in experimental membranous nephropathy.
- SP-40,40, a serum protein homologous to clusterin, inhibits MAC formation.
- Clusterin's role in passive Heymann nephritis was previously unexamined.
Purpose of the Study:
- To investigate the involvement of rat clusterin in passive Heymann nephritis.
- To determine if clusterin deposits correlate with MAC formation in this model.
Main Methods:
- Utilized an antibody to rat clusterin for immunofluorescence.
- Examined glomerular capillary walls for clusterin and complement deposits (C3, C5b-9).
- Employing complement depletion with cobra venom factor.
Main Results:
- Clusterin deposits were observed along the glomerular capillary wall, mirroring C3 and C5b-9 deposition patterns.
- Complement depletion abolished proteinuria and intraglomerular MAC formation.
- Clusterin deposits were absent in complement-depleted animals.
Conclusions:
- Rat clusterin is present in the glomerulus during passive Heymann nephritis.
- Clusterin deposition correlates with MAC formation and proteinuria.
- Clusterin may play a regulatory role in the in situ formation of the terminal complement cascade during glomerular injury.